tbuckley/cabot-search huggingface dataset:
Clinical and financial implications of ADUARA trial on a real-world population.
Authors: Bharathi Muthusamy, Emily Craig Zabor, Nathan A. Pennell
Journal: Journal of Clinical Oncology (2023)

8526 Background: In the ADAURA trial, adjuvant (adj) osimertinib improved disease free survival (DFS) in resected, EGFR-mutant ( EGFRm) Stage IB-IIIA NSCLC compared to placebo. Based on these results, the FDA approved osimertinib in the adj setting. In this study, we have evaluated the hypothetical clinical and financial effects of adj osimertinib on the early-stage, EGFRm NSCLC patients at Cleveland Clinic who were treated prior to the FDA approval. Methods: Starting in 2010, Cleveland Clinic has been performing targeted molecular testing in all resected NSCLCs. With this information, we created a database of patients from 01/2010 to 01/2021 with resected, non-squamous NSCLC. The standard of care (SOC) arm of this study consisted of patients with stage IB-IIIA, EGFRm disease from our internal database. Data for the adj osimertinib arm were obtained through a microsimulation study by first generating the per-stage DFS distribution in the SOC arm, and then applying the per-stage hazard ratios from ADAURA to obtain the parameters of the exponential DFS distribution with osimertinib treatment. Outcomes and costs, such as treatment and imaging, were directly calculated for the SOC arm based on the amount of time each patient spent in a recurrence-free or recurrent state, and whether there was CNS involvement at recurrence. Costs and outcomes were averaged across 1000 simulated datasets for the osimertinib arm. Based on ADAURA we assumed that 78.4%, 16.2%, and 5.4% of DFS events were CNS- recurrence, CNS+ recurrence, or death. Results: 1,487 patients were included in the database. 724 of these patients had stage IB-IIIA disease and EGFR testing. 82 patients were EGFRm+ (exon 19 deletion or the L858R mutation), and their survival outcomes were used in the SOC arm. At 5 years, 32 (39%) of the patients were alive and disease free. With the addition of adj osimertinib, an estimated average of 61 (71.4%) of patients would have been disease free and alive. This corresponds to an average improvement in 5-year DFS of 35.4%. The cost of testing all 724 patients would have been $2,865.80 per patient eligible for osimertinib with single-gene EGFR testing or $5,279.11 per eligible patient with targeted NGS testing. The total treatment and healthcare costs with adj osimertinib in the 82 patients would have been $49,057,952.75 or $598,267.72 per patient. With SOC (surveillance +/- adj chemotherapy + osimertinib only upon recurrence), total and per patients costs were $12,297,374.11 and $149,967.98 respectively. This corresponds to an average increase in total costs of $448,299.74 per person with the use of adj osimertinib. Conclusions: Over a decade at Cleveland Clinic, about 5.5% (82/1,487) patients with early stage NSCLC would have been affected by the adj osimertinib approval. In our simulation, we estimated adj osimertinib would have improved 5-year DFS by 35.4% (29 more patients) but with a significant financial cost of about $450,000 per eligible patient.
Association between locoregional failure and <i>NFE2L2/KEAP1/CUL3 </i>pathway mutations in NRG/RTOG 9512: A randomized trial of hyperfractionation vs. conventional fractionation in T2N0 glottic squamous cell carcinoma (SCC).
Authors: Li Guan, Pedro A. Torres-Saavedra, Xiaobei Zhao, Michael B. Major, Brittany J. Holmes, Ngan Nguyen, Parasakthy Kumaravelu, Tim Hodge, Maximilian Diehn, Jose Zevallos, Bahman Emami, Stephen M. Sagar, William H. Morrison, Christopher J. Schultz, Jimmy J. Caudell, Christopher U. Jones, Sue S. Yom, Jonathan Harris, Quynh-Thu Le, David N. Hayes
Journal: Journal of Clinical Oncology (2023)

6054 Background: Radiotherapy (RT) is the primary treatment for patients with T2N0 glottic SCC. ~30% of these patients experience locoregional relapse despite dose escalation. Mutations in the NFE2L2/KEAP1/CUL3 pathway have been linked to radioresistance preclinically and in small retrospective studies. We tested the hypothesis that patients with T2 glottic SCCs having these mutations would show radioresistance and more local (LF) and locoregional failures (LRF) when treated with RT compared to those without, using samples from a phase III trial. Methods: Of 250 randomized patients with T2N0 glottic SCC receiving definitive RT in RTOG 9512, 119 had available biospecimens that were subjected to amplicon-based next generation sequencing (appropriate to low-input DNA from biopsy specimens) to assess for presence of NFE2L2/KEAP1/CUL3 mutations without regard to outcomes. The association between binary mutation status and LF, LRF, disease-free survival (DFS), and overall survival (OS) was assessed using (cause-specific) Cox models (2-sided alpha of 0.05). LR/LRF rates were estimated by the cumulative incidence method and DFS/OS rates by the Kaplan-Meier method. Results: Nineteen of 119 patients (16.0%; 95% confidence interval [CI] 9.4, 22.6) had mutations in the NFE2L2/KEAP1/CUL3 pathway. Patient and tumor characteristics were similar between those with and without mutation.There were 32 LF, 37 LRF, and 80 DFS events, and 52 deaths. Patients with mutation compared to those without had significantly higher LF and LRF rates (Table). Median DFS was 0.9 years (95% CI 0.4, not reached) for the mutation group compared to 4.2 years (95% CI 3.2, 6.4) for those without. The hazard ratio (HR) for DFS was significantly higher for the mutated compared to the non-mutated group in the first 2 years after randomization but declined thereafter (Table), likely due to limited events after 2 years in the mutation group. There was no significant difference in OS between the two groups (HR = 0.76; 95% CI 0.35, 1.6; p = 0.48). Conclusions: NFE2L2/KEAP1/CUL3 pathway mutations may predict radiation treatment failure in T2N0 glottic cancer. They may also be a prognostic biomarker for DFS, but the current evidence supports the harmful effect of these mutations only during the first 2 years from randomization. Clinical trial information: NCT00002727 . [Table: see text]
Tumor board tuesday and awareness of novel therapies and toxicities in solid tumor oncology.
Authors: Johnathan Ebben, Alison Rothbaum, Michael J. Pishvaian
Journal: Journal of Clinical Oncology (2023)

11008 Background: Social media platforms, including Twitter, offer novel tools to accelerate discussion and learning that crosses national borders, flattens hierarchies, and enables collaborations not previously possible. Here, we report on a new initiative, Tumor Board Tuesday (TBT), which facilitates the presentation of cases with active discussion from thousands of stakeholders across the oncology community, highlighting new practice changes and precision oncology strategies. Herein, we sought to evaluate 1) the nature of participation by individuals and groups, as well as their scope of participation in TBT; 2) the impact of participation in TBT, including new collaborations forged, practice changes, increased knowledge of the use of novel agents, and their associate toxicities, as well as emerging clinical trials available to patients. Methods: TBT performed a survey designed to assess the demographics, experience, and opinions of platform users. This survey was collated with voluntary pre/post TBT presentation knowledge checks to assess knowledge acquisition. Results: Based on the survey of TBT participants (n = 38), participant gender is roughly balanced (48.4% women, 48.4% men; 3.2% prefer not to answer). 83.6% of respondents reside in the United States, 8% in Brazil, 5.4% in India, and 3% in Ireland. Interestingly, the majority of respondents identified Twitter as their primary source for oncologic and practice changing updates. Among self-identified oncologists, 12.9% identified as senior members of the field, 51.6% as mid-career, 16.1% as early career, and 12.9% as fellows/trainees. Despite the wide variation in career stage, 81.1% of respondents noted that they had become aware of a new treatment option or modality through TBT participation, which caused 78.4% to change or re-think their treatment approach. In addition, 75.7% of respondents noted that TBT had helped them to become more aware of novel agent toxicities, and 78.4% became aware of a clinical trial option because of TBT participation. Finally, 78.4% of respondents identified TBT as a tool that had helped grow professional connections and networks. On average, there were 56 respondents to knowledge-based questions within each TBT presentation. Analysis of responses to pre and post TBT questions focused on breast, GU, and pulmonary malignancies revealed a 12%, 13%, and 6% respective increase in correct answer choices. Conclusions: Social media, specifically, the use of the TBT platform engages oncology professionals across the career spectrum, enhances learning about novel therapies and corresponding toxicities, and broadens professional connections.
Antidepressant adherence trajectory before cancer diagnosis and risk of antidepressant discontinuation after cancer diagnosis among middle-aged US adults.
Authors: Oluwadamilola Onasanya, Susan dosReis, Udim Damachi, Wendy Camelo Castillo
Journal: Journal of Clinical Oncology (2023)

e18890 Background: For middle-aged adults taking antidepressants before cancer diagnosis, concerns exist about drug-drug interactions between antidepressants and antineoplastics. Clinical guidelines recommend detailed assessment of the new cancer survivor's past history of antidepressant use before considering antidepressant discontinuation. We aimed to determine whether, in real-world settings, the risk of antidepressant discontinuation after cancer diagnosis is associated with survivors’ past antidepressant adherence trajectories. Methods: A retrospective cohort of 45 to 64-year old individuals with incident cancer diagnosis (index date) and ≥2 antidepressant fills in the 9 months before index date, IQVIA PharMetrics Plus for Academics claims, 2006-2020. Antidepressant adherence in the 9-month baseline was measured as monthly proportion of days covered (PDC) before tamoxifen initiation. Group-based trajectory modeling (GBTM) was used to identify clusters of survivors with distinct antidepressant adherence trajectories pre-index date i.e., we calculated polynomial functions of monthly PDCs and compared 2 to 6-group finite mixture models to determine which model best fit the data, based on the Bayesian Information Criterion, expert-adjudged parsimony and ≥10% of the sample in each trajectory group. Antidepressant discontinuation after cancer diagnosis was defined as a 45-day gap in antidepressant supply. Survivors were censored at first of either antidepressant discontinuation, loss of enrollment or 1 year post-index date. Cox regression compared the hazard of antidepressant discontinuation by trajectory group, adjusted for demographics, mental disorder and cancer type. Results: We identified 7,293 middle-aged cancer survivors with prior antidepressant use; females 72%, mean age (SD) 56 (7) years. GBTM identified 4 adherence trajectory groups (consistently high, steady increase, declining, and recent start); metastatic cancer being characteristic of the latter 3 groups relative to the consistently high group. Antidepressant discontinuation was lowest in the consistently high group (26% [mean months-to-discontinuation: 9]) and highest in the declining (68% [5]) and recent start (51% [6]) groups, p &lt; .01. Hazard ratios [95% CI] of discontinuation were significantly higher in the declining (2.7 [2.3 – 3.2]), recent start (1.9 [1.7 – 2.0]) and steady increase (1.5 [1.4 – 1.6]) groups, relative to the consistently high group. Conclusions: Middle-aged cancer survivors with past trajectories of consistently high adherence to antidepressants experience lower risk of antidepressant discontinuation after cancer diagnosis in real-world practice. However, concern remains about the unintended health outcomes of relatively higher antidepressant discontinuation among survivors diagnosed with metastatic cancer.
The UC san diego health suspicion of cancer clinic.
Authors: Poorva Vaidya, Elena R. Cutting, Shumei Kato, William M. Mitchell, Benjamin Michael Heyman, Kathryn A. Gold
Journal: Journal of Clinical Oncology (2023)

e18528 Background: Physicians at UC San Diego Moores Cancer Center (MCC), like at many major cancer centers in the United States, are subspecialized by tumor type. Patients with symptoms concerning for cancer, but without a diagnosis, often face challenges in establishing care with an oncologist, which can potentially lead to delays in diagnosis and treatment. Methods: At our institution, we created a Suspicion of Cancer (SOC) clinic for referral of patients who have symptoms concerning for cancer, but without a definitive diagnosis of malignancy. The purpose of the clinic is to facilitate establishment of a diagnosis and access to an oncologist in a timely manner. We created an order for referral in our electronic medical record system that enables any provider to refer to patients to the SOC clinic. Once a referral is placed, a hematologist-oncologist or medical oncologist reviews the case and approves the patient for an appointment with the SOC clinic. Results: Between January 2022 and November 2022, we received 107 unique referrals to the SOC clinic. The average age of referred patients was 64 years, with 50 (46.7%) females and 57 (53.3%) males. Thirty-four (31.2%) referrals were from primary care doctors, 23 (21.5%) from hospital medicine, 22 (20.6%) from emergency medicine, 15 (14.0%) from medical subspecialties or neurology, 11 (10.3%) from surgery or surgical subspecialties, and 1 (0.93%) that was self-referred. Thirty (28.0%) patients already had definitive diagnosis of malignancy from either our institution or an outside institution, while 77 (72.0%) did not have a diagnosis at time of referral. Of the 107 referrals, 21 (19.6%) did not follow up with a medical oncologist or hematologist-oncologist within our health system. Reasons for not following up included insurance status, establishing care elsewhere, failed attempts to contact patients, or no shows to established clinic appointments. One patient was already established with a hematologist-oncologist within the MCC prior to referral. Eighty-six (80.4%) patients were seen in new consultation by a medical oncologist or hematologist-oncologist at our institution. After referral, the average time to consultation with a medical oncologist or a hematologist-oncologist was 15.3 days. In the 77 cases without diagnosis at time of referral, 39 (50.6%) underwent biopsy, while 38 (49.4%) were deemed to not require biopsy or declined biopsy. Twenty-five (32.5%) patients were diagnosed with cancer and 52 (67.5%) either did not have biopsy or had a negative biopsy. Ninety-two (86.0%) of the 107 referred patients were alive at time of analysis, while 15 (14.0%) were deceased. Conclusions: The MCC SOC clinic offers a referral pathway to expedite diagnosis and access to care for new oncology patients. In continuing to collect data related to the above outcomes, we hope to identify barriers to the delivery of oncologic care and improve patient outcomes.
Safety and serum estradiol levels in hormonal treatments for vulvovaginal atrophy in breast cancer survivors: A systematic review and meta-analysis.
Authors: Ana Carolina Carolina Marin Comini, Bruno Murad Carvalho, Matheus José Barbosa Moreira, Pedro Cotta Abrahão Reis, Luisa Colapietro, Jane Northern, Felipe Batalini
Journal: Journal of Clinical Oncology (2023)

e24049 Background: Vulvo-Vaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Methods: Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I 2 index. Results: We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67pg/ml (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p &lt; 0.001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but one study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. Conclusions: In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Fluorine-18 fluorodeoxyglucose (<sup>18</sup>FDG)-uptake assessment of PDGFRA mutant gastrointestinal stromal tumors (GIST): A retrospective multicenter Italian study.
Authors: Maria Concetta Nigro, Andrea Marchetti, Elena Fumagalli, Ida De Luca, Alexia Francesca Bertuzzi, Maria Susanna Grimaudo, Giovanni Grignani, Lorenzo D'Ambrosio, Alessandra Merlini, Ignazio Carreca, Lorena Incorvaia, Alessandra Dimino, Silvia Gasperoni, Bruno Vincenzi, Maria A. Pantaleo, Margherita Nannini
Journal: Journal of Clinical Oncology (2023)

11539 Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile. Although functional imaging with 18 FDG-PET plays a proven role in GIST, especially in early assessment tumor response, less is known about 18 FDG-uptake according to the GIST molecular subtypes. Taking into account of clinical and molecular features of D842V mutant GIST, we assumed that this subset of GIST could also have a different 18 FDG-uptake. Therefore, the aim of the present study has been to investigate the degree of FDG uptake of PDGFRA mutant GIST, focusing on D842V ones, in order to better define the role of functional imaging in this rare and peculiar subset of GIST. Methods: Patients with PDGFRA mutant GIST underwent 18 FDG-PET were retrospectively included from seven GIST Italian reference centers. Data on maximum standardized uptake (SUVmax) value of primary tumor or metastatic disease were collected. Results: 71 patients have been included: 37 (55.1%) with D842V PDGFRA mutant GIST (group A) and 34 (47.9%) with PDGFRA non-D842V mutant GIST (group B). Additionally, 30 patients with exon 11 KIT mutant GIST have been included, as control (group C). SUVmax values were obtained from primary tumor and metastatic lesions in 55 (54,4%) and 46 (45,6%) patients, respectively. Considering the whole population of 101 patients, the global median SUVmax was 3,7 (IQR 0-9.1), while the median SUVmax for group A, B, and C was 0, 3.6, and 10.4, respectively. The median SUVmax of PDGFRA mutant GIST was significantly lower than the median value of exon 11 KIT mutant GIST (p &lt; 0.001). Notably, median 18 FDG-uptake was significantly lower in D842V PDGFRA mutant GIST compared to PDGFRA non-D842V mutant ones (p = 0.021). Conclusions: PDGFRA D842V-mutant GIST present an overall lower 18 FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with 18 FDG-PET in this subset of GIST is limited. Finally, the prognostic value of the 18 FDG-uptake degree within all PDGFRA mutant GIST will be investigated in the future.
The association between systemic anticancer therapy (SACT) at the end of life (EOL) and acute care use among patients treated at oncology practices participating in the Oncology Care Model (OCM).
Authors: Maureen Canavan, Karna Sheth, Jeffrey A. Scott, Sarah Westvold, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2023)

6580 Background: Receipt of chemotherapy near EOL has been shown to harm patient and caregiver experience, increase hospitalizations, intensive care unit (ICU) and emergency department (ED) use and drive-up costs. As rates of chemotherapy at EOL have declined, we have seen increases in the rates of immunotherapy at EOL. It is unknown whether use of EOL immunotherapy is associated with the same pattern of higher downstream acute care use and cost. Using data from OCM, a Centers for Medicare and Medicaid Services (CMS) alternative payment model, we evaluated the relationship between SACT type and acute care utilization within 30 days of death. Methods: Using anonymized Integra Connect data for OCM episode claims attributed to 8 multi-site OCM practices between July 2016 and December 2021, we stratified patients by SACT type received within 30 days of death (immunotherapy (IO), chemotherapy (CT), or none) and used chi-square tests to compare the proportion of decedents who had inpatient admission, ICU stay, ED visits without inpatient admission, and hospice use within 30 days of death. Results: Among 14,169 OCM decedents, 2,227 (15.7%) received IO within 30 days of death, 6,627 (46.8%) received CT and 5,315 (37.5%) received no SACT (table). Patients who received no SACT at EOL were significantly more likely to start hospice within 30 days of death (76%) and to be in hospice for ≥3 days prior to death (61%) compared with IO (65% and 40%) and CT patients (59% and 37%) respectively (all p-values&lt;0.05). Patients who received IO or CT were significantly more likely to have an inpatient stay within 30 days of death (66% and 68% respectively) compared with patients who received no SACT at EOL (58%, p-values &lt;0.001). No difference in ED visits within 30 days of death between IO (18%), CT (20%), and no SACT (19%) p &lt; 0.270. Conclusions: Patients who received chemotherapy or IO therapy within 30 days of death had higher proportion of inpatient admissions, ICU stay and lower rates of hospice than patients who received no SACT at the EOL. Patients who did not have any SACT at EOL were more likely to utilize hospice services and for a longer time. Further research should explore whether these findings are generalizable to patients outside of OCM and the magnitude of costs associated with these acute care metrics. [Table: see text]